The main objectives are to search for the biosynthesis of tetrahydroisoquinoline (TIQ) alkaloids in animals and in man during ethanol intoxication and to delineate some of their pharmacologic properties. TIQ alkaloids arise as condensation products of catecholamines (such as dopamine, norepinephrine and epinephrine) with acetaldehyde, which is a metabolite of ethanol. Other experiments are conducted with methanol, which gives rise in vivo to formaldehyde and, in turn, to another series of TIQ alkaloids. We are interested in the potential pharmacologic actions of biosynthesized TIQ alkaloids: Do they provoke changes in neuronal function and changes in behavior during and after the ingestion of alcoholic beverages? We are also considering the possibility that TIQ alkaloids may play a role in the addictive phase of alcoholism. We have already determined that TIQ alkaloids can function as surrogate neurotransmitters in adrenergic systems. They are taken up and stored by nerve endings, they are released by stimulation, and they activate certain receptors. Current experiments are directed towards: (1) measurement of TIQs in brain and other catecholaminergic loci in intoxicated animals and (2) study of the pharmacologic properties of TIQs in adrenergic neurons and at adrenergic receptors. We are attempting to evaluate whether or not biosynthesized TIQ alkaloids can contribute to either the direct actions or the aftereffects of ingested alcoholic beverages.